Analysis of the molecular structure of lymphocyte membrane antigens and receptors holds the key to many fundamental problems in contemporary immunology. The specific aims of this research are to establish the primary structure of several human T-cell differentiation antigens (i.e., T-25, P-40, and P-16), and to establish their ontogenetic relationships and their phylogenetic relationship with the murine Thy-1 antigen. Major methodologies include amino acid sequence determination and lipid and carbohydrate analyses. Information obtained from such studies should lead to better understanding of the cell-cell, cell-antigen, and cell-lymphokine interactions that are all essential elements of the immune system. Structural comparison between the P-25 and P-16 antigens is particularly interesting because the latter is apparently associated only with suppressor T lymphocytes whereas the former is common to all T lymphocytes. Molecular differences between the two antigens are thus directly related to lymphocyte differentiation and function. Structural studies of lymphocyte surface antigens have been hampered by the small quantities of these proteins available on a per cell basis. Recently, our laboratory has succeeded in isolating milligram quantities of the mouse Thy-1 and human P-25 antigens, as well as slightly lesser amounts (i.e., hundreds of micrograms) of human P-16 and P-40 antigens, from a moderate number (approximately 10 billion) of lymphoblastoid T lymphocytes. The availability of milligram quantities of purified material, in conjunction with recent advances in protein sequencing as well as carbohydrate and lipid analyses technologies, have brought our laboratory to a favorable position to tackle the structure of the T-lymphocyte antigens. (CS)